An Open-label Study to Identify Molecular Markers of Steroid Resistance
Information source: Massachusetts General Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Nasal Polyps
Intervention: mometasone furoate (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Massachusetts General Hospital Official(s) and/or principal investigator(s): Daniel Hamilos, MD, Principal Investigator, Affiliation: Mass General Hospital
Overall contact: Lauren Tracy, BA, Phone: 617-643-2262, Email: letracy@partners.org
Summary
Aim 1: To assess steroid sensitivity to mometasone furoate (MF) in cultured nasal polyp
explant tissue in vitro.
Aim 2: To assess steroid sensitivity in vivo in each subject by comparing symptom scores,
nasal endoscopic findings before and following 4 weeks of treatment with mometasone furoate
nasal spray (MFNS) and by comparing tissue immunohistology in NP biopsies pre- and
post-treatment withA MFNS.
Aim 3: To characterize the molecular signature of gene mRNA expression in
"steroid-sensitive" and "steroid-resistant" NP using microarray on NP tissue pre- and
post-MFNS treatment.
Hypothesis 1: Genes that regulate apoptosis are dysregulated in nasal polyp (NP)
inflammatory cells, epithelial cells and smooth muscle actin myofibroblasts leading to
persistence of inflammatory cell infiltration and abnormal epithelial and myofibroblast
cellular proliferation. These can be corrected by mometasone. Apoptosis-regulating genes
that cannot be corrected by mometasone are upregulated in steroid-resistant NP.
Elucidation of this dysregulation may prove insightful in understanding the mechanism of
action of mometasone in NP and identifying potential molecular targets that will increase
steroid sensitivity or, conversely, overcome steroid resistance.
Hypothesis 2: There is a molecular signature of gene expression in NP that signifies
steroid sensitive NP (SS-NP). This signature is altered in steroid resistant NP (SR-NP).
Elucidation of differences in the molecular signature of SS-NP versus SR-NP before and after
treatment with mometasone furoate (MFNS) will provide novel insight into treatment of NP
with steroids.
Clinical Details
Official title: An Open-label Study to Identify Molecular Markers of Steroid Resistance in Nasal Polyposis Before and Following Treatment With Mometasone Furoate (MFNS) 2 Sprays/Nostril (100 Mcg/Nostril) Twice Daily for 4 Weeks.
Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: Steroid Sensitivity in vivoMolecular Signature of mRNA Steroid sensitivity in vitro
Eligibility
Minimum age: 21 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- The subject must fulfill all of the following conditions or characteristics to be
considered for enrollment:
1. Male or female between ages 21 - 70 years residing in the Boston area
2. History of chronic rhinosinusitis (symptoms for at least 3 months). Subject must have
two or more of the following:
- Facial pain/pressure or headache
- Nasal congestion
- Anterior or posterior nasal drainage
- Hyposmia/anosmia
3. Abnormal CT scan in at least 2 sinuses areas within 3 months
4. Evidence of bilateral polyps or polypoid mucosa (on nasal endoscopy) with minimum
polyp/polypoid score of 4 (see scoring system below).
Exclusion Criteria:
- 4. History of suggestive of immunodeficiency (i. e. those who have had > one
pneumonia in the past 12 months or those with known immune deficiency).
5. History of cystic fibrosis, Kartagener's syndrome, immotile cilia syndrome,
hypogammaglobulinemia or bleeding disorder
6. URI within six weeks prior to enrollment
7. Intranasal cocaine use
8. Pregnancy (if applicable
9. History of fainting
MEDICATION EXCLUSIONS prior to NP biopsies:
10. Use of prescription blood thinners
11. Use of systemic glucocorticoids for two weeks prior to enrollment
12. Use of intranasal corticosteroids and anticholinergics for three days prior to
enrollment
13. Use of an antibiotic for three days prior to enrollment
14. Use of antihistamines for one week prior to enrollment
Locations and Contacts
Lauren Tracy, BA, Phone: 617-643-2262, Email: letracy@partners.org
Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting Lauren Tracy, BA, Phone: 617-643-2262, Email: letracy@partners.org Daniel Hamilos, MD, Principal Investigator
Additional Information
Starting date: July 2013
Last updated: January 17, 2014
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